This study is concerned with the basic problem of electrolyte and nonelectrolyte transport across biological membranes. We plan to measure the permeability coefficients of a wide spectrum of hydrophilic and hydrophobic solutes with varying chemical and physical properties across biological membranes. The effect of various physio-chemical variables, such as temperature, to determine the activation energy of interaction, pH to determine the effect of membrane charge, ionic strength, to determine the effect of membrane swelling and shrinking, and mercury compounds, on these processes of permeation will also be investigated. We will also be engaged in determining the role of some important membrane constituents, such as, cholesterol, calcium ion, sulfhydryl groups, and amino groups, in the transport characteristics of cell membrane. The degree and the nature of control which glycolytic intermediates exercise on the passive movements of Na and K in mammalian red cells will be investigated. Once this interdependence is explained in basic terms, we will study the changes in these movements that occur in diseased cells. We expect to get information about the chemical and physical structure of biological membranes and about the mechanisms whereby living cells maintain their composition and ability to function. With respect to structure, we will learn more about the degree of participation of membrane protein in membrane continuity and the degree of organization of membrane lipids. Furthermore, the question of whether or not cell membrane acts both as a selective solvent and a molecular sieve will be tested directly for the first time. Functionally, we expect to identify whether diffusion through membrane interior or transition through water-membrane interface is rate-limiting for transport.